Combustion, Not Nicotine, Linked to Graves’ Disease Complications

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Key Points:

• New Study: Cureus observational study of 304 Graves’ disease patients compared combustible, heated tobacco, e-cigarette, and non-users.

• Findings: GO prevalence highest in smokers (50.8 percent), intermediate in heated tobacco users (26.7 percent), lower in non-users (21.1 percent), and lowest in e-cigarette users (8.7 percent).

• Severity: No active/moderate GO among e-cigarette users; 21.3 percent of smokers had active GO.

• Conclusion: Combustion byproducts – not nicotine – drive GO risk; “clean nicotine” delivery linked to reduced or no risk.

• Broader Evidence: 2024 and 2025 reviews confirm reduced risks (asthma, COPD, toxins) and higher quit success with e-cigs vs NRT.

• Public Health Context: Adult vaping grew 68.6 percent (2016–2023) to 20 million+ users; youth vaping at 10-year low; young adult smoking nearly gone (5.6 percent).

• Policy Implication: Evidence supports encouraging reduced-risk alternatives over restricting them.

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A study in Cureus provides further evidence that it is the combustion in tobacco products – not nicotine – that drives the harmful effects of smoking. Published in August, the observational study examined 304 adults newly diagnosed with Graves’ disease to determine whether nicotine itself, or the toxic byproducts of combustion, were responsible for the increased risk of Graves’ orbitopathy (GO). Graves’ disease is an autoimmune disorder that overstimulates the thyroid gland, leading to hyperthyroidism.

The researchers divided patients into four groups: 61 combustible cigarette users, 30 heated tobacco product users, 23 current e-cigarette users, and 190 individuals who had never used nicotine. Former smokers, pregnant or breastfeeding women, patients who had previously received treatment for GO, and those with severe comorbidities were excluded. The final cohort of 304 adults was evaluated for the prevalence and severity of GO, alongside thyroid and vitamin D laboratory measures.

Overall, 26.6 percent of patients were diagnosed with GO. Among combustible cigarette users, prevalence was highest at 50.8 percent. Heated tobacco product users reported GO at a rate of 26.7 percent, non-users at 21.1 percent, and e-cigarette users at just 8.7 percent. Importantly, there were no cases of active or moderate-to-severe GO among e-cigarette users, whereas 21.3 percent of combustible cigarette users reported active GO, compared to 10 percent of heated tobacco users and 6.3 percent of non-users.

The authors concluded that their findings “suggest how tobacco combustion byproducts, rather than nicotine itself, may be the key drivers of GO pathogenesis. The low GO prevalence in [e-cigarette users] supports the hypothesis that clean nicotine delivery might carry reduced or no risk.” Notably, e-cigarette users reported the lowest prevalence of GO – even lower than non-nicotine users – while heated tobacco product use was associated with intermediate risk, consistent with reduced but not eliminated combustion exposure.

This adds to a growing body of evidence that eliminating combustion significantly reduces the harms associated with nicotine use. A 2024 review of existing studies concluded that e-cigarette use was linked to reduced risks, including lower odds of asthma, COPD, and oral disease, compared to smoking. Similarly, a 2025 Cochrane review found that people who switched from combustible cigarettes to e-cigarettes had substantially lower levels of exposure to toxins and carcinogens present in tobacco smoke. That review also confirmed that e-cigarettes are more effective than traditional nicotine replacement therapy in helping adults quit smoking.

These findings reaffirm what tobacco researcher Michael Russell declared more than 50 years ago: people smoke for the nicotine, but die from the tar. Since then, researchers and manufacturers have worked to create alternatives that deliver nicotine while reducing the harms of smoking for those unable or unwilling to quit entirely.

E-cigarettes entered the U.S. market in 2007 and have since grown significantly in popularity among adults, many of whom are current or former smokers. Between 2016 and 2023, the number of adults who vape increased by 68.6 percent, adding 8.9 million people to reach more than 20 million current users in 2023. Meanwhile, youth vaping has fallen to a 10-year low, cigarette smoking among adults continues to decline, and smoking among young adults – the largest e-cigarette user group – is nearly nonexistent, with only 5.6 percent of 18- to 24-year-olds smoking in 2023.

Policymakers should welcome these findings, which reinforce that e-cigarettes are safer than combustible cigarettes. As the evidence base continues to expand, policies must encourage the use of reduced-risk alternatives while monitoring unintended consequences, rather than restricting access to products that can help accelerate declines in smoking.

Nothing in this analysis is intended to influence the passage of legislation, and it does not necessarily represent the views of Tobacco Harm Reduction 101.